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Translational Research: the Journal of Laboratory and Clinical Medicine

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https://www.readbyqxmd.com/read/28802867/novel-single-cell-technologies-in-acute-myeloid-leukemia-research
#1
REVIEW
Soumyasri Das Gupta, Zohar Sachs
Acute myeloid leukemia (AML) is a lethal malignancy because patients who initially respond to chemotherapy eventually relapse with treatment refractory disease. Relapse is caused by leukemia stem cells (LSCs) that reestablish the disease through self-renewal. Self-renewal is the ability of a stem cell to produce copies of itself and give rise to progeny cells. Therefore, therapeutic strategies eradicating LSCs are essential to prevent relapse and achieve long-term remission in AML. AML is a heterogeneous disease both at phenotypic and genotypic levels, and this heterogeneity extends to LSCs...
July 25, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28797549/predicting-thyroid-nodule-malignancy-at-several-prevalence-values-with-a-combined-bethesda-molecular-test
#2
Hélène Lasolle, Benjamin Riche, Myriam Decaussin-Petrucci, Emmanuelle Dantony, Véronique Lapras, Catherine Cornu, Joël Lachuer, Jean-Louis Peix, Jean-Christophe Lifante, Oana-Maria Capraru, Samia Selmi-Ruby, Bernard Rousset, Françoise Borson-Chazot, Pascal Roy
OBJECTIVE: Investigation of thyroid nodules using fine-needle aspiration cytology (FNAC) gives indeterminate results in up to 30% of samples using the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). We present a combined Bethesda-molecular predictor of nodule malignancy to improve the accuracy of the preoperative diagnosis of thyroid nodules. DESIGN: The study sought to detect a molecular signature of thyroid nodule malignancy. METHODS: A molecular test was performed on FNACs from 128 thyroid nodules from prospectively included patients, collected in a tertiary center...
July 22, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28784428/large-scale-3-dimensional-quantitative-imaging-of-tissues-state-of-the-art-and-translational-implications
#3
REVIEW
Seth Winfree, Michael J Ferkowicz, Pierre C Dagher, Katherine J Kelly, Michael T Eadon, Timothy A Sutton, Troy A Markel, Mervin C Yoder, Kenneth W Dunn, Tarek M El-Achkar
Recent developments in automated optical sectioning microscope systems have enabled researchers to conduct high resolution, three-dimensional (3D) microscopy at the scale of millimeters in various types of tissues. This powerful technology allows the exploration of tissues at an unprecedented level of detail, while preserving the spatial context. By doing so, such technology will also enable researchers to explore cellular and molecular signatures within tissue and correlate with disease course. This will allow an improved understanding of pathophysiology and facilitate a precision medicine approach to assess the response to treatment...
July 22, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28774752/deciphering-metabolic-rewiring-in-breast-cancer-subtypes
#4
REVIEW
Martin P Ogrodzinski, Jamie J Bernard, Sophia Y Lunt
Metabolic reprogramming, an emerging hallmark of cancer, is observed in breast cancer. Breast cancer cells rewire their cellular metabolism to meet the demands of survival, proliferation, and invasion. However, breast cancer is a heterogeneous disease, and metabolic rewiring is not uniform. Each subtype of breast cancer displays distinct metabolic alterations. Here, we focus on unique metabolic reprogramming associated with subtypes of breast cancer, as well as common features. Therapeutic opportunities based on subtype-specific metabolic alterations are also discussed...
July 15, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28755873/chimeric-antigen-receptor-t-cell-therapy-for-glioblastoma
#5
REVIEW
Analiz Rodriguez, Christine Brown, Behnam Badie
Chimeric antigen receptor (CAR) T-cell therapy has shown great promise in the treatment of hematological disease, and its utility for treatment of solid tumors is beginning to unfold. Glioblastoma continues to portend a grim prognosis and immunotherapeutic approaches are being explored as a potential treatment strategy. Identification of appropriate glioma-associated antigens, barriers to cell delivery, and presence of an immunosuppressive microenvironment are factors that make CAR T-cell therapy for glioblastoma particularly challenging...
July 15, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28764956/microbiome-and-metabolome-data-integration-provides-insight-into-health-and-disease
#6
REVIEW
Michael Shaffer, Abigail J S Armstrong, Vanessa V Phelan, Nichole Reisdorph, Catherine A Lozupone
For much of our history, the most basic information about the microbial world has evaded characterization. Next-generation sequencing has led to a rapid increase in understanding of the structure and function of host-associated microbial communities in diverse diseases ranging from obesity to autism. Through experimental systems such as gnotobiotic mice only colonized with known microbes, a causal relationship between microbial communities and disease phenotypes has been supported. Now, microbiome research must move beyond correlations and general demonstration of causality to develop mechanistic understandings of microbial influence, including through their metabolic activities...
July 14, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28755872/new-approaches-for-the-enhancement-of-chimeric-antigen-receptors-for-the-treatment-of-hiv
#7
REVIEW
Mayra A Carrillo, Anjie Zhen, Jerome A Zack, Scott G Kitchen
HIV infection continues to be a life-long chronic disease in spite of the success of antiretroviral therapy (ART) in controlling viral replication and preventing disease progression. However, because of the high cost of treatment, severe side effects, and inefficiency in curing the disease with ART, there is a call for alternative therapies that will provide a functional cure for HIV. Cytotoxic T lymphocytes (CTLs) are vital in the control and clearance of viral infections and therefore immune-based therapies have attempted to engineer HIV-specific CTLs that would be able to clear the infection from the body...
July 14, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28754419/evaluation-of-tolerance-to-lentiviral-lv-rpe65-gene-therapy-vector-after-subretinal-delivery-in-nonhuman-primates
#8
Alexandre Matet, Corinne Kostic, Alexis-Pierre Bemelmans, Alexandre Moulin, Serge G Rosolen, Samia Martin, Fulvio Mavilio, Vazrik Amirjanians, Knut Stieger, Birgit Lorenz, Francine Behar-Cohen, Yvan Arsenijevic
Several approaches have been developed for gene therapy in RPE65-related Leber congenital amaurosis. To date, strategies that have reached the clinical stages rely on adeno-associated viral vectors and two of them documented limited long-term effect. We have developed a lentiviral-based strategy of RPE65 gene transfer that efficiently restored protein expression and cone function in RPE65-deficient mice. In this study, we evaluated the ocular and systemic tolerances of this lentiviral-based therapy (LV-RPE65) on healthy nonhuman primates (NHPs), without adjuvant systemic anti-inflammatory prophylaxis...
July 8, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28746860/integrating-rna-sequencing-into-neuro-oncology-practice
#9
REVIEW
David S Rogawski, Nicholas A Vitanza, Angela C Gauthier, Vijay Ramaswamy, Carl Koschmann
Malignant tumors of the central nervous system (CNS) cause substantial morbidity and mortality, yet efforts to optimize chemo- and radiotherapy have largely failed to improve dismal prognoses. Over the past decade, RNA sequencing (RNA-seq) has emerged as a powerful tool to comprehensively characterize the transcriptome of CNS tumor cells in one high-throughput step, leading to improved understanding of CNS tumor biology and suggesting new routes for targeted therapies. RNA-seq has been instrumental in improving the diagnostic classification of brain tumors, characterizing oncogenic fusion genes, and shedding light on intratumor heterogeneity...
July 8, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28719799/mesencephalic-astrocyte-derived-neurotrophic-factor-manf-a-new-player-in-endoplasmic-reticulum-diseases-structure-biology-and-therapeutic-roles
#10
Yeawon Kim, Sun-Ji Park, Ying Maggie Chen
Mesencephalic astrocyte-derived neurotrophic factor (MANF), a newly identified 18-kDa soluble protein, localizes to the luminal endoplasmic reticulum (ER), whose stress can stimulate MANF expression and secretion. In Drosophila and zebrafish, MANF regulates dopaminergic neuron development. In contrast, in mice, MANF deficiency leads to diabetes and activation of the unfolded protein response. Recent studies in rodent models have demonstrated that MANF mitigates diabetes, exerts neurotrophic function in neurodegenerative disease, protects cardiomyocytes and neurons in myocardial infarction and cerebral ischemia, respectively, and promotes immune cell phenotype switch from proinflammatory macrophages to prorepair anti-inflammatory macrophages...
June 29, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28719798/chimeric-antigen-receptor-t-cells-for-b-cell-malignancies
#11
REVIEW
Eben I Lichtman, Gianpietro Dotti
The adoptive transfer of T-lymphocytes modified to express chimeric antigen receptors (CAR-Ts) has produced impressive clinical responses among patients with B-cell malignancies. This has led to a rapid expansion in the number of clinical trials over the past several years. Although CD19-specific CAR-Ts are the most extensively evaluated, CAR-Ts specific for other B-cell-associated targets have also shown promise. However, despite this success, toxicities associated with CAR-T administration remain a significant concern...
June 29, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28686852/integrated-meta-omic-analyses-of-the-gastrointestinal-tract-microbiome-in-patients-undergoing-allogeneic-hematopoietic-stem-cell-transplantation
#12
Anne Kaysen, Anna Heintz-Buschart, Emilie E L Muller, Shaman Narayanasamy, Linda Wampach, Cédric C Laczny, Norbert Graf, Arne Simon, Katharina Franke, Jörg Bittenbring, Paul Wilmes, Jochen G Schneider
In patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), treatment-induced changes to the gastrointestinal tract (GIT) microbiome have been linked to adverse outcomes, most notably graft-versus-host disease (GvHD). However, it is presently unknown whether this relationship is causal or consequential. Here, we performed an integrated meta-omic analysis to probe deeper into the GIT microbiome changes during allo-HSCT and its accompanying treatments. We used 16S and 18S rRNA gene amplicon sequencing to resolve archaea, bacteria, and eukaryotes within the GIT microbiomes of 16 patients undergoing allo-HSCT for the treatment of hematologic malignancies...
June 20, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28688236/antigen-specific-regulatory-t-cells-are-police-cars-the-answer
#13
REVIEW
Nicholas A J Dawson, Megan K Levings
Cellular therapy with T-regulatory cells (Tregs) is a promising strategy to control immune responses and restore immune tolerance in a variety of immune-mediated diseases, such as transplant rejection and autoimmunity. Multiple clinical trials are currently testing this approach, typically by infusing a single dose of polyclonal Tregs that have been expanded in vitro. However, evidence from animal models of Treg therapy has clearly shown that antigen-specific Tregs are vastly superior to polyclonal cells, meaning that fewer cells are needed for the desired therapeutic effect...
June 19, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28683259/rna-seq-analysis-of-peripheral-blood-mononuclear-cells-reveals-unique-transcriptional-signatures-associated-with-disease-progression-in-dengue-patients
#14
Arup Banerjee, Shweta Shukla, Abhay Deep Pandey, Saptamita Goswami, Bhaswati Bandyopadhyay, Vishnampettai Ramachandran, Shukla Das, Arjun Malhotra, Amitesh Agarwal, Srima Adhikari, Mehebubar Rahman, Shatakshee Chatterjee, Nemai Bhattacharya, Nandita Basu, Priyanka Pandey, Vikas Sood, Sudhanshu Vrati
Patients infected with Dengue virus usually present a mild, self-limiting febrile dengue infection (DI) that occasionally leads to a potentially lethal complication, called the severe dengue (DS). The ability to identify the prognostic markers of DS could allow an improved disease intervention and management. To identify the transcriptional signatures associated with the dengue disease progression, we carried out the high-throughput sequencing of the RNA isolated from the peripheral blood mononuclear cells (PBMCs) of the dengue patients of varying severity and compared with that in the patients with other febrile illnesses (OFIs) or the healthy controls...
June 17, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28675806/the-future-perspective-metabolomics-in-laboratory-medicine-for-inborn-errors-of-metabolism
#15
REVIEW
Yana Sandlers
Metabolomics can be described as a simultaneous and comprehensive analysis of small molecules in a biological sample. Recent technological and bioinformatics advances have facilitated large-scale metabolomic studies in many areas, including inborn errors of metabolism (IEMs). Despite significant improvements in the diagnosis and treatment of some IEMs, it is still challenging to understand how genetic variation affects disease progression and susceptibility. In addition, a search for new more personalized therapies and a growing demand for tools to monitor the long-term metabolic effects of existing therapies set the stage for metabolomics integration in preclinical and clinical studies...
June 15, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28668522/the-traumatic-bone-trauma-induced-heterotopic-ossification
#16
REVIEW
Devaveena Dey, Benjamin M Wheatley, David Cholok, Shailesh Agarwal, Paul B Yu, Benjamin Levi, Thomas A Davis
Heterotopic ossification (HO) is a common occurrence after multiple forms of extensive trauma. These include arthroplasties, traumatic brain and spinal cord injuries, extensive burns in the civilian setting, and combat-related extremity injuries in the battlefield. Irrespective of the form of trauma, heterotopic bone is typically endochondral in structure and is laid down via a cartilaginous matrix. Once formed, the heterotopic bone typically needs to be excised surgically, which may result in wound healing complications, in addition to a risk of recurrence...
June 15, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28668521/lipidomics-in-translational-research-and-the-clinical-significance-of-lipid-based-biomarkers
#17
REVIEW
Daniel J Stephenson, L Alexis Hoeferlin, Charles E Chalfant
Lipidomics is a rapidly developing field of study that focuses on the identification and quantitation of various lipid species in the lipidome. Lipidomics has now emerged in the forefront of scientific research due to the importance of lipids in metabolism, cancer, and disease. Using both targeted and untargeted mass spectrometry as a tool for analysis, progress in the field has rapidly progressed in the last decade. Having the ability to assess these small molecules in vivo has led to better understanding of several lipid-driven mechanisms and the identification of lipid-based biomarkers in neurodegenerative disease, cancer, sepsis, wound healing, and pre-eclampsia...
June 15, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28651075/modulation-of-natriuretic-peptide-receptors-in-human-adipose-tissue-molecular-mechanisms-behind-the-natriuretic-handicap-in-morbidly-obese-patients
#18
Alessandra Gentili, Maria Rosaria Frangione, Elisa Albini, Carmine Vacca, Maria Anastasia Ricci, Stefano De Vuono, Marcello Boni, Fabio Rondelli, Luciana Rotelli, Graziana Lupattelli, Ciriana Orabona
The B-type natriuretic peptide (BNP) hormone plays a crucial role in the regulation of cardiovascular and energy homeostasis. Obesity is associated with low circulating levels of BNP, a condition known as "natriuretic handicap." Recent evidences suggest an altered expression of BNP receptors-both the signaling natriuretic peptide receptors (NPR)-A and the clearance NPR-C receptor-in adipose tissue (AT) as one of the putative causes of natriuretic handicap. The current study aims at clarifying the molecular mechanisms behind the natriuretic handicap, focusing on NPR modulation in the AT of obese and control subjects...
June 10, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28648487/development-of-novel-avenues-to-overcome-challenges-facing-car-t-cells
#19
REVIEW
Soyeon Kim, Edmund K Moon
There has been dramatic success in treating patients with adoptive transfer of autologous T cells genetically modified to express a chimeric antigen receptor redirecting them to the antigen CD19. Despite this success, the application of chimeric antigen receptor T-cell therapy in solid malignancies has encountered many challenges that need to be overcome if similar success across other cancers is to become a reality. These challenges can be classified into 6 categories: the heterogeneity of tumor cell clones and tumor-associated antigen expression; poor T-cell trafficking into the tumor site; poor T-cell survival and persistence; the presence of suppressive immune cells; the secretion of suppressive soluble factors in the tumor microenvironment; and the upregulation of T-cell intrinsic inhibitory pathways...
June 10, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28651074/chimeric-antigen-receptor-engineered-natural-killer-and-natural-killer-t-cells-for-cancer-immunotherapy
#20
REVIEW
Dominique Bollino, Tonya J Webb
Natural killer (NK) cells of the innate immune system and natural killer T (NKT) cells, which have roles in both the innate and adaptive responses, are unique lymphocyte subsets that have similarities in their functions and phenotypes. Both cell types can rapidly respond to the presence of tumor cells and participate in immune surveillance and antitumor immune responses. This has incited interest in the development of novel cancer therapeutics based on NK and NKT cell manipulation. Chimeric antigen receptors (CARs), generated through the fusion of an antigen-binding region of a monoclonal antibody or other ligand to intracellular signaling domains, can enhance lymphocyte targeting and activation toward diverse malignancies...
June 9, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
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